title: Resequencing, haplotype construction and identification of novel variants of CYP2D6 in Mexican Mestizos.
abstract: OBJECTIVE
  The CYP2D6 enzyme participates in the metabolism of commonly prescribed drugs: antidepressants, antipsychotics and antihypertensives. The CYP2D6 gene shows a high degree of interindividual and interethnic variability that influences its expression and function. Mexican Mestizos are a recently admixed population resulting from the combination of Amerindian, European and, to a lesser extent, African populations. This study aimed to comprehensively characterize the CYP2D6 gene in Mexican Mestizos.
  
  
  METHODS
  We performed linkage disequilibrium and network analyses in resequencing data of 96 individuals from two regions within Mexico with a different history of admixture and particular population dynamics, the Northwestern state of Sonora and the Central-Pacific state of Guerrero.
  
  
  CONCLUSIONS
  We identified 64 polymorphisms, including 14 novel variants: 13 SNPs and a CYP2D7 exon 2 conversion, that was assigned CYP2D6*82 by the Human Cytochrome P450 (CYP) Allele Nomenclature Committee. Three novel SNPs were predicted to have functional effects. For CYP2D6*82 we hypothesize an Amerindian origin that is supported by its identification in three Mexican Amerindian groups (Mayas, Tepehuanos and Mixtecos). Frequencies of CYP2D6*1, *2, *4, *5, *10, *29, *53, *82 and its duplications were 50.0, 25.5, 14.1, 2.0, 2.6, 1.0, 0.5, 2.1 and 3.6%, respectively. We found significant frequency differences in CYP2D6*1 and *2 between Mexican Mestizos and in CYP2D6*1, *2, *4, *5, *10 and *29 between Mexicans and at least one other population. We observed strong linkage disequilibrium and phylogenetic relationships between haplotypes. To our knowledge, this study is the first comprehensive resequencing analysis of CYP2D6 in Mexicans or any other Latin American population, providing information about genetic diversity relevant in the development of pharmacogenomics in this region.
authors.affiliation: National Institute of Genomic Medicine (MEXICO), Periférico Sur 4124 Torre Zafiro II Piso 6, Col. Ex-Rancho de Anzaldo, Mexico DF 01900, Mexico.
authors.forename: Alejandra V
authors.initials: AV
authors.lastname: Contreras
authors.forename: Tulia
authors.initials: T
authors.lastname: Monge-Cazares
authors.forename: Luis
authors.initials: L
authors.lastname: Alfaro-Ruiz
authors.forename: Salvador
authors.initials: S
authors.lastname: Hernandez-Morales
authors.forename: Haydee
authors.initials: H
authors.lastname: Miranda-Ortiz
authors.forename: Karol
authors.initials: K
authors.lastname: Carrillo-Sanchez
authors.forename: Gerardo
authors.initials: G
authors.lastname: Jimenez-Sanchez
authors.forename: Irma
authors.initials: I
authors.lastname: Silva-Zolezzi
mesh_terms: D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007198:Indians, North American / Q000208:ethnology / Q000235:genetics*; D008800:Mexico / Q000208:ethnology
chemical_list: D019389:Cytochrome P-450 CYP2D6